Older Adult Frequent 9-1-1 Callers for Emergency Medical Services in a Large Metropolitan City: Individual- and System-Level Considerations.

BACKGROUND: High utilizers of 9-1-1 place a substantial burden on emergency medical services (EMS). Results of a retrospective review of records data of the City of Los Angeles Fire Department (LAFD) showed a significant increase in older adult high utilizers of 9-1-1. OBJECTIVE: The objective of this study was to explore individual- and system-level factors implicated in EMS use among older adults, and to provide system recommendations to mitigate overuse. METHODS: A phenomenological study was conducted, drawing from LAFD EMS records between 2012 and 2016 to identify and contact high-utilizing patients older than 50 years, their family, agency representatives, and LAFD personnel. Interviews were recorded, transcribed, and coded and a thematic analysis was completed. RESULTS: We conducted in-depth interviews with 27 participants, including patients (n = 8), their families (n = 6), social service agency representatives (n = 3), and LAFD personnel (n = 10). The following cross-cutting themes emerged: nature of 9-1-1 calls, barriers to access, and changing the system. In addition, LAFD and social service agency representatives identified the role of EMS responders and social agency representatives. Patients and their families agreed that previous encounters and interactions with emergency care responders were relevant factors. CONCLUSIONS: This study described reasons for 9-1-1 calls related to medical and social service needs, including mental health care. Our analysis offers insight from different stakeholders' perspectives on access to medical care and types of barriers that interfere with medical care. All groups shared recommendations to advance access to medical and mental health care.

Urine biomonitoring of occupational exposure to methotrexate using a highly sensitive UHPLC-MS/MS method in MRM3 mode.

Methotrexate (MTX) is widely used as antineoplastic drug (AD) and as an immunosuppressive. As a result, many healthcare professionals are exposed to this drug which is classified as dangerous to handle due to its reproductive toxicity in humans. Since the 1990 s, cases of internal contamination of professionals handling this molecule have been reported in the literature and even recently MTX was detected in the urine of professionals. To date, there is no toxicological reference value for occupational exposure to MTX. Given the toxicity of this molecule, the internal contamination of professionals must be reduced and kept as low as possible according to the ALARA principle (as low as reasonably achievable). The aim of this work was to develop an UHPLC-MS/MS method in MRM (Multiple Reaction Monitoring) and MRM3 modes for routine application in MTX occupational biomonitoring. Good linearity (r greater than 0.997), precision (CV < 15 %), and accuracy (94.97-97.80% of the nominal value in MRM mode; 105.90-112.25% in MRM3 mode) were achieved. This method is reliable with high specificity and high sensitivity especially in MRM3 mode and has better LOD and LLOQ (1 ng/L and 2.5 ng/L) than published methods to date. The MRM3 mode increases the signal-to-noise ratio compared to the MRM mode. It was then applied routinely for the biological monitoring of healthcare professionals exposed to methotrexate. One hundred and seventeen urine samples from 93 healthcare professionals occupationally exposed to methotrexate were analyzed. Fifteen healthcare professionals (16.1 %) were found to be contaminated with methotrexate. Urine concentration levels ranged from 2.5 to 380 ng/L with a median value of 8.9 ng/L. Such efficient analytical tool is essential for the routine biological monitoring of healthcare professionals exposed to methotrexate. It also enables the traceability of occupational exposure to this molecule and the evaluation of the effectiveness of preventive measures such as individual and collective protective equipment.

Nurses' internal contamination by antineoplastic drugs in hospital centers: a cross-sectional descriptive study.

OBJECTIVE: The aim of this study was to assess internal antineoplastic drugs (ADs) contamination in the nursing staff in French hospital centers, using highly sensitive analytical methods. METHODS: This cross-sectional study included nurses practicing in care departments where at least one of the five ADs studied was handled (5-fluorouracil, cyclophosphamide, doxorubicin, ifosfamide, methotrexate). The nurses study participation lasted 24 h including collection of three urine samples and one self-questionnaire. All urine samples were assayed by ultra-high-performance liquid chromatography-tandem mass spectrometry methods with very low value of the lower limit of quantification (LLOQ). RESULTS: 74 nurses were included, 222 urine samples and 74 self-questionnaires were collected; 1092 urine assays were performed. The percentage of nurses with internal AD contamination was 60.8% and low levels of urinary concentrations were measured. Regarding nurses with internal contamination (n = 45), 42.2% presented internal contamination by methotrexate, 37.8% by cyclophosphamide, 33.3% by ifosfamide, 17.8% by 5-fluorouracil metabolite and 6.7% by doxorubicine. Among the positive assays, 17.9% (n = 26/145) were not explained by exposure data from the self-questionnaire but this could be due to the skin contact of nurses with contaminated work surfaces. CONCLUSIONS: This study reported high percentage of nurses with internal ADs contamination. The low LLOQ values of the used analytical methods, allowed the detection of ADs that would not have been detected with the current published methods: the percentage of contamination would have been 17.6% instead of the 60.8% reported here. Pending toxicological reference values, urine ADs concentrations should be reduced as low as reasonably achievable (ALARA principle).

Effect of a Coordinated Community and Chronic Care Model Team Intervention vs Usual Care on Systolic Blood Pressure in Patients With Stroke or Transient Ischemic Attack: The SUCCEED Randomized Clinical Trial.

Importance: Few stroke survivors meet recommended cardiovascular goals, particularly among racial/ethnic minority populations, such as Black or Hispanic individuals, or socioeconomically disadvantaged populations. Objective: To determine if a chronic care model-based, community health worker (CHW), advanced practice clinician (APC; including nurse practitioners or physician assistants), and physician team intervention improves risk factor control after stroke in a safety-net setting (ie, health care setting where all individuals receive care, regardless of health insurance status or ability to pay). Design, Setting, and Participants: This randomized clinical trial included participants recruited from 5 hospitals serving low-income populations in Los Angeles County, California, as part of the Secondary Stroke Prevention by Uniting Community and Chronic Care Model Teams Early to End Disparities (SUCCEED) clinical trial. Inclusion criteria were age 40 years or older; experience of ischemic or hemorrhagic stroke or transient ischemic attack (TIA) no more than 90 days prior; systolic blood pressure (BP) of 130 mm Hg or greater or 120 to 130 mm Hg with history of hypertension or using hypertensive medications; and English or Spanish language proficiency. The exclusion criterion was inability to consent. Among 887 individuals screened for eligibility, 542 individuals were eligible, and 487 individuals were enrolled and randomized, stratified by stroke type (ischemic or TIA vs hemorrhagic), language (English vs Spanish), and site to usual care vs intervention in a 1:1 fashion. The study was conducted from February 2014 to September 2018, and data were analyzed from October 2018 to November 2020. Interventions: Participants randomized to intervention were offered a multimodal coordinated care intervention, including hypothesized core components (ie, ≥3 APC clinic visits, ≥3 CHW home visits, and Chronic Disease Self-Management Program workshops), and additional telephone visits, protocol-driven risk factor management, culturally and linguistically tailored education materials, and self-management tools. Participants randomized to the control group received usual care, which varied by site but frequently included a free BP monitor, self-management tools, and linguistically tailored information materials. Main Outcomes and Measures: The primary outcome was change in systolic BP at 12 months. Secondary outcomes were non-high density lipoprotein cholesterol, hemoglobin A1c, and C-reactive protein (CRP) levels, body mass index, antithrombotic adherence, physical activity level, diet, and smoking status at 12 months. Potential mediators assessed included access to care, health and stroke literacy, self-efficacy, perceptions of care, and BP monitor use. Results: Among 487 participants included, the mean (SD) age was 57.1 (8.9) years; 317 (65.1%) were men, and 347 participants (71.3%) were Hispanic, 87 participants (18.3%) were Black, and 30 participants (6.3%) were Asian. A total of 246 participants were randomized to usual care, and 241 participants were randomized to the intervention. Mean (SD) systolic BP improved from 143 (17) mm Hg at baseline to 133 (20) mm Hg at 12 months in the intervention group and from 146 (19) mm Hg at baseline to 137 (22) mm Hg at 12 months in the usual care group, with no significant differences in the change between groups. Compared with the control group, participants in the intervention group had greater improvements in self-reported salt intake (difference, 15.4 [95% CI, 4.4 to 26.0]; P = .004) and serum CRP level (difference in log CRP, -0.4 [95% CI, -0.7 to -0.1] mg/dL; P = .003); there were no differences in other secondary outcomes. Although 216 participants (89.6%) in the intervention group received some of the 3 core components, only 35 participants (14.5%) received the intended full dose. Conclusions and Relevance: This randomized clinical trial of a complex multilevel, multimodal intervention did not find vascular risk factor improvements beyond that of usual care; however, further studies may consider testing the SUCCEED intervention with modifications to enhance implementation and participant engagement. Trial Registration: ClinicalTrials.gov Identifier: NCT01763203.

A highly sensitive UHPLC-MS/MS method for urine biological monitoring of occupational exposure to anthracycline antineoplastic drugs and routine application.

Anthracycline antineoplastic drugs (doxorubicin, epirubicin, daunorubicin) are "hazardous drugs for handling" by healthcare professionals. To monitor their occupational exposure, a highly sensitive ESI-UHPLC-MS/MS method for the assay of anthracyclines in urine was developed. The urine extraction consisted of SPE extraction method. A good linearity (r > 0.996), precision (CV < 14.4%), and accuracy (bias < 13.6%) were achieved for the three drugs. The lower limit of quantification (LOQ) was 10 ng/L. This LOQ value is equal to the LOQ of published methods except for epirubicin, for which the LOQ value is better by a factor of 10 (best published LOQ value: 100 ng/L). Applying this method in routine, more than 77 healthcare professionals occupationally exposed to anthracyclines were monitored and 77 urines were analyzed. Two healthcare professionals (2.6%) were found to be contaminated to doxorubicin and/or epirubicin. The measured concentrations ranged from 17.7 to 218 ng/L. Such an efficient analytical tool, combining both high specificity and sensitivity is essential for reliable highlight of contamination during biological monitoring of healthcare professionals widely exposed to these drugs. This anthracycline antineoplastic drugs exposure monitoring allows healthcare professionals for assessing effectiveness individual and collective protective measures and for ensuring traceability of occupational exposure to these drugs.

Study protocol for the assessment of nurses internal contamination by antineoplastic drugs in hospital centres: a cross-sectional multicentre descriptive study.

INTRODUCTION: Antineoplastic drugs (AD) are potentially carcinogenic and/or reprotoxic molecules. Healthcare professionals are increasingly exposed to these drugs and can be potentially contaminated by them. Internal contamination of professionals is a key concern for occupational physicians in the assessment and management of occupational risks in healthcare settings. Objectives of this study are to report AD internal contamination rate in nursing staff and to identify factors associated with internal contamination. METHODS AND ANALYSIS: This trial will be conducted in two French hospital centres: University Hospital of Bordeaux and IUCT-Oncopole of Toulouse. The target population is nurses practicing in one of the fifteen selected care departments where at least one of the five studied AD is handled (5-fluorouracil, cyclophosphamide, doxorubicin, ifosfamide, methotrexate). The trial will be conducted with the following steps: (1) development of analytical methods to quantify AD urine biomarkers, (2) study of the workplace and organization around AD in each care department (transport and handling, professional practices, personal and collective protection equipments available) (3) development of a self-questionnaire detailing professional activities during the day of inclusion, (4) nurses inclusion (urine samples and self-questionnaire collection), (5) urine assays, (6) data analysis. ETHICS AND DISSEMINATION: The study protocol has been approved by the French Advisory Committee on the Treatment of Information in Health Research (CCTIRS) and by the French Data Protection Authority (CNIL). Following the opinion of the Regional Committee for the Protection of Persons, this study is outside the scope of the provisions governing biomedical research and routine care (n°2014/87). The results will be submitted to peer-reviewed journals and reported at suitable national and international meetings. TRIAL REGISTRATION NUMBER: NCT03137641.

Biomonitoring of occupational exposure to 5-FU by assaying α-fluoro-ß-alanine in urine with a highly sensitive UHPLC-MS/MS method.

5-Fluorouracil (5-FU) is one of the most widely used antineoplastic drugs handled by healthcare professionals (HCP). To monitor occupational exposure to 5-FU, a highly sensitive ESI-UHPLC-MS/MS method was developed for the assay of its main human metabolite, α-fluoro-ß-alanine (FBAL), in urine. After a derivatization step, solid phase extraction was used for the urine. Good linearity (r > 0.996), precision (CV < 14.76%), and accuracy (bias < 12.16%) were achieved. The lower limit of quantification (LOQ), 20 pg ml-1, is the lowest one published to date. Seven urine samples from 73 HCP exposed to 5FU were positive for FBAL, indicating 5FU contamination (9.6%). FBAL urine concentrations ranged from 25 to 301 pg ml-1. Such an efficient analytical tool combining high specificity with high sensitivity is essential for the reliable detection and routine biological monitoring of healthcare professionals occupationally exposed to this widely used antineoplastic drug. This method allows biomonitoring of occupational exposure to 5-fluorouracil in a routine manner, with the aim of assessing the effectiveness of collective and individual protective measures.

Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED).

BACKGROUND: Recurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population. METHODS/DESIGN: In this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP <130 mmHg) at 1 year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care. DISCUSSION: If this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01763203 .

Highly sensitive LC-MS/MS methods for urinary biological monitoring of occupational exposure to cyclophosphamide, ifosfamide, and methotrexate antineoplastic drugs and routine application.

Highly sensitive ESI-LC-MS/MS methods were developed for urinary biological monitoring of occupational exposure to cyclophosphamide (CP), ifosfamide (IF), and methotrexate (MTX), which are hazardous antineoplastic drugs frequently handled by healthcare professionals. Extraction methods consisted of liquid/liquid extraction for simultaneous urinary CP and IF assays, and of solid phase extraction for the urinary MTX assay. A good linearity (r2>0.997), precision (CV<14.6%), and accuracy (bias<9.9%) were achieved for all compounds. The limit of detection (LOD) was 10pg/ml and the lower limit of quantification (LOQ) was 20pg/ml for all three drugs. Applying these methods in routine, more than 116 healthcare professionals occupationally exposed to antineoplastic drugs were monitored and 635 urines were analysed. Eleven healthcare professionals (9.5%) were found to be contaminated to at least one of the three antineoplastic drugs. Among analysed urines, 22 samples were found positives. The measured concentrations ranged from 20.1 to 1850pg/ml and, for six samples, concentrations were at CP trace level, between the LOD and LOQ values (10-20pg/ml). Such efficient analytical tools combining high specificity with high sensitivity are essential for reliable detection and routine biological monitoring of healthcare professionals occupationally exposed to these widely used antineoplastic drugs. These methods allow to monitor the healthcare professionals exposure to antineoplastic drugs in the aim to assess the effectiveness of collective and individual protective measures.

Adverse childhood experiences, health perception, and the role of shared familial factors in adult twins.

To examine the relationship between adverse childhood experiences (ACE) and health perception in adulthood, and to explore the contribution of shared familial factors to these associations. Data were collected from 180 female twins (90 pairs) from the community-based University of Washington Twin Registry. Participants completed questionnaires including the modified ACE Questionnaire, Traumatic Life Events Questionnaire, McGill Pain Questionnaire-Short Form, and the SF-36. Mixed effects linear regression modeling investigated the effects of ACE on indices of health perception controlling for correlated twin data. Additional models examined the associations while controlling for the experience of physical and/or sexual abuse in childhood; within-twin pair models that inherently adjust for familial factors explored shared familial influences. After controlling for relevant demographic variables, more ACE was associated with worse perceptions of general health (p=.01) and vitality (p=.05) on the SF-36. After controlling for childhood physical and/or sexual abuse, the relationship between ACE and general health remained significant (p=.01) while vitality was no longer significant. None of the associations remained significant after accounting for the influence of familial factors. These results support previous findings on the negative link between ACE and perceived health in adulthood. The detrimental effects of ACE on vitality may be accounted for by the experience of childhood physical and/or sexual abuse. Shared familial factors might play a partial role in the relationship between ACE and health perception. Future research should further investigate the genetic and environmental mechanisms that may explain this relationship.

Quantification methods of folpet degradation products in plasma with HPLC-UV/DAD: application to an in vivo toxicokinetic study in rats.

Solid-phase extractions followed by HPLC-UV/DAD methods were developed for occupational biological monitoring or forensic investigations of the fungicide folpet using its degradation products, phthalimide and phthalamic acid as plasma biomarkers. These methods show good linearity (r>0.9955), precision (CV<15%) and accuracy (bias<14.8%). The lower limits of quantification for phthalimide and phthalamic acid were 10 and 20 ng/ml and the absolute recoveries were higher than 86% and 68%, respectively. Applying these methods, a plasma toxicokinetic study of folpet in rats after intratracheal administration of Folpan 80WG showed that inhalation of folpet could be a route of exposure with an important systemic absorption.

Physicochemical characteristics and bronchial epithelial cell cytotoxicity of Folpan 80 WG(R) and Myco 500(R), two commercial forms of folpet.

BACKGROUND: Pesticides, in particular folpet, have been found in rural and urban air in France in the past few years. Folpet is a contact fungicide and has been widely used for the past 50 years in vineyards in France. Slightly water-soluble and mostly present as particles in the environment, it has been measured at average concentration of 40.1 mug/m3 during its spraying, 0.16-1.2 mug/m3 in rural air and around 0.01 mug/m3 in urban air, potentially exposing both the workers and the general population. However, no study on its penetration by inhalation and on its respiratory toxicity has been published. The objective of this study was to determine the physicochemical characteristics of folpet particles (morphology, granulometry, stability) in its commercial forms under their typical application conditions. Moreover, the cytotoxic effect of these particles and the generation of reactive oxygen species were assessed in vitro on respiratory cells. RESULTS: Granulometry of two commercial forms of folpet (Folpan 80WG(R) and Myco 500(R)) under their typical application conditions showed that the majority of the particles (>75%) had a size under 5 mum, and therefore could be inhaled by humans. These particles were relatively stable over time: more than 75% of folpet remained in the particle suspension after 30 days under the typical application conditions. The inhibitory concentration (IC50) on human bronchial epithelial cells (16HBE14o-) was found to be between 2.89 and 5.11 mug/cm2 for folpet commercial products after 24 h of exposure. Folpet degradation products and vehicles of Folpan 80 WG(R) did not show any cytotoxicity at tested concentrations. At non-cytotoxic and subtoxic concentrations, Folpan 80 WG(R) was found to increase DCFH-DA fluorescence. CONCLUSION: These results show that the particles of commercial forms of folpet are relatively stable over time. Particles could be easily inhaled by humans, could reach the conducting airways and are cytotoxic to respiratory cells in vitro. Folpet particles may mediate its toxicity directly or indirectly through ROS-mediated alterations. These data constitute the first step towards the risk assessment of folpet particles by inhalation for human health. This work confirms the need for further studies on the effect of environmental pesticides on the respiratory system.

Myocardium distribution of sertindole and its metabolite dehydrosertindole in guinea-pigs.

Sertindole, like other atypical antipsychotics, has been shown to increase the action potential duration and QT interval in a concentration dependent manner, in in vitro electrophysiological studies. However, this does not always translate into increased duration of the QT interval, increased risk of torsade de pointes or sudden death in clinical practice. The reasons for these apparent discrepancies are unclear and many studies have underscored the importance of the interpretation of in vitro electrophysiological data in the context of other pharmacodynamic (e.g. cardiac ion channels target, receptor affinity) and pharmacokinetic parameters (total plasma drug concentration and drug distribution). To address the possible relevance of the concentrations used in experimental studies, the myocardium distribution of sertindole and its metabolite was determined after single and repeated intraperitoneal administration to guinea-pigs. The data suggest that the plasma concentration appears to predict the concentration in the myocardium and that the myocardium concentrations of sertindole are 3.1 times higher than plasma concentrations. Using these data, the relevance of in vitro electrophysiological studies to clinical plasma concentrations has been appraised.

Pharmacologically induced relaxation of tracheal smooth muscle is increased in hyperoxia-exposed 15-day-old rats.

Hyperoxia increases maximum airway contractility in newborn guinea pigs and immature rats. Studies examining the mechanisms of hyperoxia-induced airway hyperresponsiveness have focused on contractile mechanisms, although excessive airway narrowing could be due to impaired relaxation. Our objective was to determine the effects of hyperoxia on airway structure and relaxing properties in juvenile rats exposed to an inspired fraction of oxygen (FiO(2)) of 0.5 within 24 hr of birth for 15 days, compared to a control group of air-exposed rats. We studied the 1) tracheal smooth muscle surface area; and 2) in vitro relaxation in precontracted (carbachol, 1.10(-3) M) isolated tracheal rings to increasing cumulative concentrations (10(-8) to 10(-4) M) of salbutamol. There was no significant difference in the amount of smooth muscle between the hyperoxia and air-exposed groups. Maximal relaxation of the isolated trachea to salbutamol was greater in the hyperoxia group than in the air-exposed group when normalized to smooth muscle surface area (-12.69 +/- 3.51 g/mm(2) vs. - 8.49 +/- 1.67 g/mm(2); P (MANOVA) < 0.05) or expressed as maximal relaxation induced by 10(-3) M theophylline (61% vs. 28%; P < 0.05). In conclusion, salbutamol-induced relaxation is enhanced (and not impaired) in newborn rats exposed to prolonged moderate hyperoxia.